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Kazinol C from Broussonetia kazinoki stimulates autophagy via endoplasmic reticulum stress-mediated signaling

Authors
Lee, YunkyeongKwon, JunheeJeong, Ji HyeRyu, Jae-HaKim, Keun Il
Issue Date
2-Jan-2022
Publisher
TAYLOR & FRANCIS LTD
Keywords
Kazinol C; endoplasmic reticulum stress; unfolded protein response; autophagy; apoptosis
Citation
ANIMAL CELLS AND SYSTEMS, v.26, no.1, pp.28 - 36
Journal Title
ANIMAL CELLS AND SYSTEMS
Volume
26
Number
1
Start Page
28
End Page
36
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/145946
DOI
10.1080/19768354.2021.2023628
ISSN
1976-8354
Abstract
Autophagy modulators are considered putative therapeutic targets because of the role of autophagy in cancer progression. Kazinol C, a 1,3-diphenylpropane from the plant Broussonetia kazinoki, has been shown to induce apoptosis in colon cancer cells through the activation of AMPK at high concentrations. In the present study, we found that Kazinol C induced autophagy through endoplasmic reticulum stress-mediated unfolded protein response signaling in several normal and cancer cell lines at low concentrations of Kazinol C that did not induce apoptosis. Kazinol C activated the transducers of unfolded protein response signaling, leading to target gene expression, LC3-II conversion, and TFEB nuclear translocation. Chemical inhibition of endoplasmic reticulum stress reduced LC3-II conversion. In addition, blockade of autophagy by knockout of Atg5 or treatment with 3-MA enhanced Kazinol C-induced apoptosis. In summary, we have uncovered Kazinol C as a novel autophagy inducer and confirmed the role of autophagy as a cellular stress protector.
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이과대학 (생명시스템학부)
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